Breathing control using high flow respiration assistance

ABSTRACT

High flow therapy is used to treat Cheyne-Stokes respiration and other types of periodic respiration disorders by periodic application of high flow therapy, adjustment of high flow therapy flow rates and/or periodic additions of CO2 or O2 into the air flow provided to the patient.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

The present application is a national phase of PCT Application No.PCT/NZ2014/000105, filed Jun. 5, 2014 titled Breathing Control Usinghigh Flow Respiration Assistance, which claims priority benefit under 35U.S.C. § 119(e) to U.S. Provisional Patent Application Ser. No.61/831,411, filed Jun. 5, 2013, titled Breathing Control Using NasalHigh Flow and Carbon Dioxide; U.S. Provisional Patent Application Ser.No. 61/982,718, filed Apr. 22, 2014, titled Breathing Control Using HighFlow Respiration Assistance; and any and all applications for which aforeign or domestic priority claim is identified in the Application DataSheet as filed with the present application. Each of the foregoing arehereby incorporated by reference under 37 CFR 1.57.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to high flow breathing therapy.More particularly, the present disclosure relates to controlling a levelof residual carbon dioxide within a patient.

BACKGROUND

High flow airway respiratory support delivers a high flow of respiratorygas to a patient. In some configurations, the high flow of respiratorygas can be delivered via a nasal cannula. The supplied respiratory gascan be heated to near body temperature. In some configurations, thesupplied respiratory gas can be humidified. In some such configurations,the supplied respiratory gas can be humidified to a saturation point.

In high flow therapy, the respiratory gas is delivered at flow ratesthat meet or exceed the patient's inspiratory flow rate (for example, insome embodiments, in excess of 12 liters per minute). For some forms ofhigh flow therapy, a source of oxygen can be blended with compressedair. Hospitals usually have 50 psi compressed oxygen and air availablefor therapeutic use. Accordingly, air can be delivered or an oxygenblender can be used to deliver blends of air and oxygen. The deliveredgas can be heated, generally to about 37° C., and can be humidified tonear 100% relative humidity (RH) using a humidifier. The gas can betransported to the patient through a heated delivery tube to reducecooling and condensation of the water vapor that has been added to therespiratory gases.

In some configurations, high flow therapy employs nasal cannulastogether with a system designed to deliver high flow rates. In suchconfigurations, the nasal cannula can have a small diameter such thatthe nasal cannula does not occlude more than about 50% of the nares. Bylimiting the occlusion of the nares, outward flow can occur duringexhalation, which allows end-expiratory CO₂ to be flushed from thenasopharyngeal cavity. This also produces resistance to expiration,which increases the length of time for expiration and decreases therespiration rate. With nasal high flow therapy, the clinician candeliver higher FiO₂ to the patient than is possible with typical oxygendelivery therapy and without the use of a non-rebreather mask ortracheal intubation.

SUMMARY

The present disclosure describes the use of high flow therapy to assistpatients who are suffering from specific respiratory disorders. In anembodiment, the disclosure describes diagnosing a specific breathingdisorder and periodically applying high flow therapy in order to treatthe breathing disorder. In an embodiment, the breathing disorder isCheyne-Stokes Respiration (CSR).

In an embodiment, the present disclosure describes making use of varyingthe delivery of high flow therapy to manipulate the amount of rebreathedCO₂. The delivery, adjustment and/or removal of high flow therapy istargeted at specific phases of the CSR cycle or other respiratorydisorders. This is designed to manipulate the amount of CO₂ in theanatomical dead space of a patient and therefore manipulate the amountof CO₂ that is rebreathed during critical times of the CSR cycle orother respiratory disorders. By targeting delivery of high flow therapyduring critical phases of the CSR cycle or other respiratory disordercycles, the fluctuation of PaCO₂ at the lungs can be stabilizedresulting in normal respiration.

In an embodiment, the present disclosure describes sensing acharacteristic of a breathing pattern and initiating a sequence toincrease carbon dioxide rebreathing. Increasing carbon dioxiderebreathing can be accomplished by decreasing flow during high flowtherapy, capturing expelled CO₂ for rebreathing and/or increasing acarbon dioxide content ratio in a breathing gas being supplied to theuser.

In an embodiment, a method of treating Cheyne-Stokes Respiration (CSR)is disclosed. The method includes measuring a signal indicative ofrespiration of a patient, analysing the signal to determine if thesignal indicates that the patient is suffering from CSR and applying ahigh flow therapy to the patient. In an embodiment, the method caninclude analysing the signal to determine if the signal indicates thatthe patient is suffering from CSR includes analysing the signal forperiods of shallow breathing or apneas in between periods of heavybreathing or hyperventilation. In an embodiment, analysing the signal todetermine if the signal indicates that the patient is suffering from CSRincludes analysing the signal for periods of a waxing respirationportion and a waning respiration portion. In an embodiment, applying thenasal high flow occurs during a transition between the waxing portionand the waning portion. In an embodiment, the method includesidentifying a period and phases of the signal indicative of therespiration of the patient. In an embodiment, initiating the nasal highflow occurs during at least one of the phases. In an embodiment, themethod includes identifying a phase delay associated with chemoreceptorsignals of the patient. In an embodiment, initiating the nasal high flowincorporates the phase delay. In an embodiment, a periodic signalamplitude having a 90% reduction of a normal signal amplitude isindicative of CSR. In an embodiment, a signal amplitude having anapproximately 50% reduction from a normal signal amplitude is indicativeof CSR. In an embodiment, the amplitude continues for about 10 secondsor more. In an embodiment, the high flow is about 40 litres per minute.In an embodiment, the method further includes humidifying air used inthe high flow therapy. In an embodiment, the high flow therapy is nasalhigh flow therapy. In an embodiment, the high flow therapy is appliedfor a window of time less than or approximately equal to the period ofthe CSR cycle. In an embodiment, measuring is performed by a sensor. Inan embodiment, analysing is performed by a hardware processor. In anembodiment, the applying is performed by a high flow respiratoryassistance device.

In an embodiment, a system for treating Cheyne-Stokes Respiration (CSR)is disclosed. The system includes a flow source configured to provide ahigh flow of respiratory gas, a non-sealing interface in fluidcommunication with the flow source, a sensor configured to sense abreathing amplitude and generate a breathing amplitude signal, and acontroller configured to receive the breathing amplitude signal from thesensor, identify respiration indicative of CSR, and control the flow ofgas based on the identification of the respiration indicative of CSR. Inan embodiment, the system also includes a humidifier in fluidcommunication with and between the flow source and the interface. In anembodiment, the system performs the method described above.

In an embodiment, a method of treating respiratory disorders using highflow respiratory assistance is disclosed. The method includesidentifying a respiratory disorder, determining a transition between awaxing period and a waning period of the respiratory disorder, applyingtherapeutic high flow therapy, and evaluating the effectiveness of thetherapy. In an embodiment, the respiratory disorder is Cheyne-StokesRespiration. In an embodiment, the therapeutic high flow therapy isnasal high flow therapy. In an embodiment, applying high flow therapyincludes applying high flow therapy periodically. In an embodiment,applying the high flow therapy includes applying high flow therapyintermittently. In an embodiment, applying high flow therapy includesapplying high flow therapy cyclically. In an embodiment, applying thehigh flow therapy includes changing a flow rate. In an embodiment,applying the high flow therapy includes using a mixture of air and CO2.In an embodiment, applying high flow therapy includes using a mixture ofair and O2. In an embodiment, applying high flow therapy includes usinga mixture of air and CO2. In an embodiment, the method is performedusing a high flow respiratory assistance device. In an embodiment, thehigh flow respiratory assistance device is a nasal high flow device. Inan embodiment, the high flow respiratory assistance device includes atleast one sensor and at least one controller.

In an embodiment, a system which provides respiratory assistance usinghigh flow therapy is disclosed. The system includes a non-sealed maskconfigured to capture expired CO₂, a high flow source configured toprovide respiratory gas to a patient through the non-sealed mask, atleast one sensor configured to measure a breathing parameter of apatient, and a controller configured to receive information from thesensor indicative of the breathing parameter and determine when to applythe high flow source to the patient through the non-sealed mask. In anembodiment, the high flow source is configured to flush expired CO2 fromthe non-sealed mask. In an embodiment, the high flow source isconfigured to flush expired CO2 from respiratory dead space of thepatient.

In an embodiment, a method of treating a respiratory disorder isdisclosed. The method includes determining a phase delay procedure forapplying high flow therapy to treat a respiratory disorder and applyinghigh flow therapy according to the phase delay procedure. In anembodiment, the method also includes evaluating an effectiveness of thehigh flow therapy. In an embodiment, evaluating the effectivenessincludes determining if the respiratory disorder has improved. In anembodiment, the method also includes adjusting the phase delay procedurebased on the evaluation. In an embodiment, a phase delay of the phasedelay procedure is increased over time. In an embodiment, a phase delayof the phase delay procedure is decreased over time. In an embodiment, aphase delay of the phase delay procedure is phased in over a period oftime. In an embodiment, the period of time is one of an hour, night,session or set of sessions. In an embodiment, the respiratory disorderis Cheyne-Stokes breathing. In an embodiment, a phase delay of the phasedelay procedure is a time delay from the detection of a decrease orincrease in tidal flow of breathing of the patient to an increase ordecrease in a flow of gases delivered to an interface of the patient. Inan embodiment, a magnitude of a flow of gases delivered to a patient isoscillated. In an embodiment, the oscillation is based on a period ofoscillation of breathing of the patient. In an embodiment, theoscillation tracks the shape of the oscillatory breathing of thepatient. In an embodiment, a peak flow delivered to the patient may beadjusted using a scaling factor based on a difference between a maximumand minimum patient breathing tidal flow. In an embodiment, the scalingfactor is constant. In an embodiment, a phase delay of the phase delayprocedure varies between zero degrees and three hundred and sixtydegrees. In an embodiment, a phase delay of the phase delay procedurevaries between zero and one hundred and eighty degrees. In anembodiment, a phase delay of the phase delay procedure varies betweenzero and forty five degrees.

In an embodiment, a system configured to treat a respiratory disorder isdisclosed. The system includes a sensor configured to determine anindication of a respiratory pattern of a patient, a hardware controllerconfigured to receive the indication of the respiratory pattern of thepatient and determine a phase delay procedure for applying high flowtherapy to treat a respiratory disorder, and a flow generator,controlled by the hardware controller, the flow generator configured toprovide a high flow therapy to the patient, wherein the hardwarecontroller controls the flow generator to provide a high flow therapyaccording to the determined phase delay procedure. In an embodiment, thehardware controller is further configured to evaluate an effectivenessof the high flow therapy. In an embodiment, evaluating the effectivenessincludes determining if the respiratory disorder has improved. In anembodiment, the hardware controller is further configured to adjust thephase delay procedure based on the evaluation. In an embodiment, a phasedelay of the phase delay procedure is increased over time. In anembodiment, a phase delay of the phase delay procedure is decreased overtime. In an embodiment, a phase delay of the phase delay procedure isphased in over a period of time. In an embodiment, the period of time isone of an hour, night, session or set of sessions. In an embodiment, therespiratory disorder is Cheyne Stokes breathing. In an embodiment, aphase delay of the phase delay procedure is a time delay from adetection of a decrease or increase in tidal flow of breathing of thepatient to an increase or decrease in a flow of gases delivered to aninterface of the patient. In an embodiment, a magnitude of a flow ofgases delivered to the patient is oscillated. In an embodiment, theoscillation is based on a period of oscillation of the patient'sbreathing. In an embodiment, the oscillation tracks the shape of theoscillatory breathing of the patient. In an embodiment, a peak flowdelivered to the patient may be adjusted using a scaling factor based ona difference between a maximum and minimum patient breathing tidal flow.In an embodiment, the scaling factor is constant. In an embodiment, aphase delay of the phase delay procedure varies between zero degrees andthree hundred and sixty degrees. In an embodiment, a phase delay of thephase delay procedure varies between zero and one hundred and eightydegrees. In an embodiment, a phase delay of the phase delay procedurevaries between zero and forty five degrees.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects and advantages of the presentdisclosure will be described with respect to the following figures.

FIG. 1A is a graph illustrating a flow signal of normal respiration.

FIG. 1B is a graph illustrating a flow signal of Cheyne-StokesRespiration.

FIG. 2 illustrates a graph of the phase delay of sensing CO₂ levelsassociated with a patient's chemoreceptors associated with Cheyne-StokesRespiration.

FIG. 3 is a graphical depiction of steady state combinations of carbondioxide and ventilation.

FIG. 4 is another graphical depiction of steady state combinations ofcarbon dioxide and ventilation.

FIG. 5 is a hardware diagram of an embodiment of a high flow respirationtherapy system.

FIG. 6A illustrates a residual CO₂ levels in a cross section of deadspace within a patient's respiration pathways during normal unaidedrespiration.

FIG. 6B illustrates a residual CO₂ levels in a cross section of deadspace within a patient's respiration pathways while using high flowtherapy.

FIG. 7 illustrates graphs indicating the periodic application of highflow therapy and its resulting effects on CO₂ levels in the body.

FIG. 8 illustrates another embodiment of the periodic application ofhigh flow therapy.

FIG. 9 illustrates a flow diagram of an embodiment of a high flowtherapy treatment for respiratory disorders

FIG. 10 illustrates a flow diagram of an embodiment of therapeutic highflow therapy application for treating CSR using a phase delay procedure.

FIG. 11 illustrates an embodiment of a non-sealing mask useful tocatching expired CO₂.

DETAILED DESCRIPTION

Respiration is believed to be regulated by central chemoreceptors in thebrain, peripheral chemoreceptors in the aortic and carotid body (locatedin the heart and neck respectively) and mechanoreceptors locatedthroughout the body. The peripheral chemoreceptors are believed torespond to both oxygen (O₂) and carbon dioxide (CO₂) partial pressureswhereas the central chemoreceptors are believed to respond only to CO₂partial pressures. The partial pressure of carbon dioxide (PaCO₂) istightly controlled as it is linked to acidity (pH) in the human body,which needs to be maintained at a constant level for proper organfunction. Pulmonary ventilation varies linearly with increases in PaCO₂but it is not until PaO₂ is reduced to below 60 mmHg (approximately 88%SaO₂) that ventilation is significantly stimulated as a response toprevent hypoxia. This is consistent with the oxygen-hemoglobindissociation curve which, due to its sigmoid shape, illustrates that theincrease of oxyhemoglobin saturation with an increase of PaO₂ isrelatively small above a PaO₂ of approximately 60 mmHg. Below the 60mmHg threshold oxyhemoglobin saturation changes much more significantlywith changes in PaO₂.

The complete respiratory control system is complex and depending on howthe system is viewed, any number of congestive heart failure (CHF)related consequences can lead to oscillations of ventilation, especiallywhen combined with sleep/wake transitions due to arousals. A simplemodel that can lead to periodic breathing is based around changes inventilation between the sleep and awake states. When a healthy personenters NREM sleep, there is a reduction in central respiratory drive, aloss of nonchemical wakefulness drive, and metabolic control dominates.These factors typically result in a decreased minute ventilation and anincreased PaCO₂. As long as PaCO₂ remains greater than the apneicthreshold (defined as the level of PaCO₂ below which rhythmic breathingceases) rhythmic breathing continues. A flow signal representing anormal or healthy breathing pattern is illustrated in FIG. 1A. Somepatients, however, particularly those with CHF, tend not to increasetheir PaCO₂ upon entering sleep resulting in a PaCO₂ close to the apneicthreshold, predisposing them to central apnea. Consider a hypocapnic CHFpatient. When the patient enters sleep, if the patient's PaCO₂ does notrise and is below the hypocapnic apnea threshold, ventilation ceases andan apnea results. The apnea produces an increase in PaCO₂ and a decreasein PaO₂ sufficient to force the respiratory drive past the arousalthreshold and the patient wakes from sleep. The arousal results inhyperventilation due to the reinstitution of the nonchemical wakingdrive and increased chemical drive to breath. The patient then returnsto sleep and the cycle repeats. This type of apnea/hyperventilationrespiration cycle is referred to as Cheyne-Stokes Respiration (CSR).

FIG. 1A illustrates a flow signal indicative of Cheyne-Stokesrespiration. CSR is characterized by a waxing period of progressivelydeeper and sometimes faster breathing or hyperventilation, followed by awaning period having a gradual decrease that results in very shallowbreaths that may include hypopneas or apneas. The pattern repeats, witheach cycle usually taking 30 seconds to 2 minutes. The pattern,therefore, can be considered an oscillation of ventilation between apneaor hypopnea and hyperventilation with a crescendo-decrescendoventilation pattern. As described above, CSR is generally associatedwith changing serum partial pressures of oxygen and carbon dioxide.

Cheyne-Stokes breathing has been recognized to occur in a highpercentage of patients suffering from CHF. The pathophysiology ofCheyne-Stokes breathing can be summarized as apnea leading to increasedcarbon dioxide, which causes excessive compensatory hyperventilation, inturn causing decreased carbon dioxide, which causes apnea, restartingthe cycle. A graphical illustration of such a breathing pattern can befound in the diagrams of FIG. 1B.

More complex models can use control system theory to model therespiratory system as a feedback control system and to make predictionsregarding the appearance of Cheyne-Stokes respiration. Linear stabilityanalysis shows that a system with a high loop gain will result inCheyne-Stokes type breathing. The response to transient changes inventilation are inappropriately magnified due to an abnormally increasedloop gain, potentially as a result of increased chemoreceptorsensitivity, low functional residual capacity or other factors. Theresult of this inappropriate response is oscillations in the minuteventilation by under and overshooting the equilibrium point.

Time delays in the system also promote instability. Time delays in thesystem promote oscillation via “hunting” type behavior and canultimately result in a negative feedback system behaving as a positivefeedback system which is equivalent to the high loop gain systemdiscussed above. In CHF patients increased circulation time, due toreduced cardiac output, increases time delays between changes inventilation and detection of PaCO₂ and PaO₂ by chemoreceptors and hencecan promote Cheyne-Stokes Respiration (CSR). As shown in FIG. 2, PaCO₂levels at the lungs rise and fall out of phase with the waxing andwaning cycles indicative of CSR. Although PaCO2 levels at the lungs willbe out of phase with the breathing pattern, PaCO₂ levels at thechemoreceptors will have an additional phase delay by as much as or morethan 180 degrees with the waxing and waning cycles. The additional phasedelay is caused by the time it takes the blood from the lungs to reachthe central (brain) chemoreceptor and the peripheral (neck)chemoreceptors.

As an example of how excessively high loop gain can cause breathinginstabilities, consider a sleeping patient that has a need to reducetheir ventilation. The control system's excessively high loop gain doesnot cause a gradual reduction in ventilation, but rather causes a morerapid decrease in ventilation which results in an overshooting of PaCO₂above the desired set point. As PaCO₂ has overshot its required target,ventilation increases and the cycle either repeats indefinitely or thepatient wakes up resetting the system. This is in contrast to a systemwith a normal loop gain which, assuming the patient doesn't wake up,would result in the oscillations damping out towards a stableequilibrium point.

More complex models of respiration can use non-linear dynamical modelsand the mathematical theory of bifurcations to predict the presence ofHopf bifurcations and limit cycles. If a Hopf bifurcation exists in asystem, a stable steady state point of a system can potentially evolveinto a stable oscillating limit cycle and vice versa. Using this conceptCSR can spontaneously appear and disappear given a transient change inlung volume, ventilation-perfusion ratio, feedback control gain,transport delay, left heart volume, lung congestion or cardiovascularefficiency.

As mentioned above, in normal respiratory control, negative feedbackbased on PaCO₂ levels allows a steady level of alveolar gasconcentrations to be maintained. Therefore, stable tissue levels ofoxygen and carbon dioxide exist. At steady state, the rate of productionof carbon dioxide equals the net rate at which it is exhaled from thebody, which (assuming no carbon dioxide in the ambient air) is theproduct of the alveolar ventilation and the end-tidal carbon dioxideconcentration. Because of this interrelationship, the set of possiblesteady states forms a hyperbola as shown in FIG. 3: Alveolarventilation=body CO₂ production/end-tidal CO₂ fraction.

In FIG. 3, this relationship is the curve falling from the top left tothe bottom right. Only positions along this curve permit the body'scarbon dioxide production to be exactly compensated for by exhalation ofcarbon dioxide. Meanwhile, there is another curve, shown in the figurefor simplicity as a straight line from bottom left to top right, whichis the body's ventilatory response to different levels of carbondioxide. Where the curves cross is a potential steady state (S).

Through respiratory control reflexes, any small transient fall inventilation (A) leads to a corresponding small rise (A′) in alveolarcarbon dioxide concentration, which is sensed by the respiratory controlsystem so that there is a subsequent small compensatory rise inventilation (B) above its steady state level (S) that helps restorecarbon dioxide back to its steady state value. In general, transient orpersistent disturbances in ventilation, carbon dioxide or oxygen levelscan be counteracted by the respiratory control system in this way.

However, as discussed above, in some pathological states, the feedbackis more powerful than is necessary to simply return the system towardsits steady state. Instead, ventilation overshoots and can generate anopposite disturbance to the original disturbance. If this secondarydisturbance is larger than the original, the next response will be evenlarger, and so on, until very large oscillations have developed, asshown in FIG. 4.

The cycle of enlargement of disturbances reaches a limit when successivedisturbances are no longer larger, which occurs when physiologicalresponses no longer increase linearly in relation to the size of thestimulus. The most obvious example of this is when ventilation falls tozero—it cannot be any lower. Thus Cheyne-Stokes respiration can bemaintained over periods of many minutes or hours with a repetitivepattern of waxing and waning respiration.

The end of the linear decrease in ventilation in response to falls incarbon dioxide is not, however, at apnea. The end occurs whenventilation is so small that air being breathed in never reaches thealveolar space because the inspired tidal volume is no larger than thevolume of the large airways, such as the trachea. Consequently, at thenadir of periodic breathing, ventilation of the alveolar space may beeffectively zero; the easily-observable counterpart of this is failureat that time point of the end-tidal gas concentrations to resemblerealistic alveolar concentrations.

Based upon an understanding of the body's reaction to carbon dioxideconcentration, it is desired to integrate into a breathing apparatus analgorithm and method for delivering a high flow of respiratory gaseswhile also providing the capability to control breathing either byentrainment of respiratory gas containing carbon dioxide and/or byvarying of carbon dioxide re-breathing from anatomical or apparatus deadspace. Breathing or re-breathing of carbon dioxide causes the patient torespond with deeper breathing, which helps control an overall breathingprofile. In some configurations, certain features, aspects andadvantages of the development can be used in periodic types ofrespiration, such as Cheyne-Stokes, in central sleep apnea and in otherforms of disturbances of breathing. In some configurations, if ashallower breath pattern is being detected, then the patient can beencouraged to take a deeper breath by temporarily increasing the levelof carbon dioxide rebreathing.

In general, high flow treatment clears anatomical dead space and can beused to control breathing. High flow therapy is usually a non-sealed oropen system, allowing excess air to be vented to out to the ambient air,rather than forced into the patient. One type of high flow treatment isnasal high flow treatment. The flow can range from less than about 1liter per minute to as much or more than about 100 liters per minute. Inan embodiment, the flow can be about 40 liters per minute. One range offlows can be about 10 liters per minute to about 40 liters per minute.The high flow of gas can be used, for example, to flush expired orresidual CO₂ from anatomical dead spaces of a patient. This processhelps to reduce or substantially eliminate residual CO₂ in a patient'srespiratory system. This reduction in residual CO₂ in nasal cavity deadspace increases ventilation efficiency by increasing the amount ofoxygen reaching the lungs in a given breath. One commercially availableexample of a high flow nasal therapy device is the Airvo™ commerciallyavailable from Fisher and Paykel Healthcare of Auckland, NZ.

FIG. 5 illustrates an embodiment of a system 500 suitable for high flowtherapy. The high flow therapy system of FIG. 5 includes a flow source501 such as, for example, a blower, a generator, a hospital source, orother high flow air source. The system includes a controller 503 forcontrolling the flow source. For example, this can be a processor orother electrical and/or mechanical system which controls the flowsource. The controller can provide a variable speed, a variable settingblower, or valve system to control how and/or when flow is applied. Inan embodiment, the system includes a non-sealing interface 505, such as,for example, a nasal cannula in fluid communication with the flow sourceto direct the flow source into the patient's respiratory system.Optionally, in some embodiments, the system can include a humidifier 507in fluid communication with the flow source and the interface. Thehumidifier humidifies the air before it is provided to the patient inorder to provide greater comfort and assistance to the patient. Thesystem also includes at least one sensor or detection mechanism 509 fordetermining the respiration of the patient and/or changes in air flow.This can be a flow sensor, a pressure sensor or a determination based onthe motor speed of the flow source. In some embodiments, an abdominaland/or thoracic band(s) can be used with the system to provideinformation on the patient's respiration. Other sensors can includevisual or acoustic measurements including optics, such as lasers, orpiezoelectric acoustic sensors.

The controller is configured to manage the operation of the flow sourceby receiving feedback from the sensor indicative of the flow of thesystem and/or respiration of the patient. The controller can beconfigured to identify or detect a CSR pattern or other abnormalbreathing pattern and control the operation of the flow source tocompensate for the abnormal breathing. The purpose of the controloperation is to aid the patient in returning to a normal breathingpattern by regulating the high flow source in such a way that thepatient's body regulates itself back to a normal breathing pattern. Thiscan be done by timing an initiation of a flow source, adjustment a flowrate of a flow source or the stopping a flow source. The application ofthe flow source to assist the patient is described in greater detailbelow.

Variable high flow, and in particular, nasal high flow, is described,for example, PCT Application No. PCT/NZ2014/000041 filed Mar. 14, 2014and hereby incorporated by reference in its entirety. Variable high flowcan be focused on the dead space clearance and can be controlled inorder to stabilize breathing in such conditions as periodicCheyne-Stokes respiration by increasing or decreasing dead spaceclearance and/or entrainment of carbon dioxide and/or oxygen to thebreathing gas. The dead space clearance of high flow therapy isillustrated below in FIGS. 6A and 6B. In some configurations, flow canbe turned on or off at different periods of inspiration or expiration.Similarly, the flow can be increased or decreased or the inspiratoryand/or expiratory profile of flow can be altered to control dead spaceclearance from upper airways of a patient.

Nasal high flow can be delivered either itself or with a hybrid maskinterface, such as those described in WO2011/078703, filed Dec. 22,2010, which claims priority to U.S. Provisional Patent Application No.61/289,544, filed Dec. 23, 2009, each of which is hereby incorporated byreference in its entirety, or in a combination of nasal prongs with anon-sealed mask, nasal pillow or hood to increase apparatus dead spacewhen nasal flow is decreased. An increase of flow can increase deadspace clearance and can reduce carbon dioxide re-breathing while adecrease of flow can increase re-breathing of carbon dioxide.

FIG. 6A illustrates a cross section of a respiratory tract, includingdead space cavities 601. As the patient breaths out, expiration 603leaves the respiration system, however, residual expiration 605 is leftin the cavities. The residual expiration 605 is shown in dark grey toillustrate a relatively high CO₂ content. The residual expiration 605 isthen sucked back into the lungs with the next inspiration. This resultsin a higher CO₂ concentration and a lower O₂ concentration than might befound in the ambient air. FIG. 6B illustrates the same cross section ofanatomical space as FIG. 6A, however, FIG. 6B illustrates the effect ofnasal high flow therapy during the same point in the respiration cycle.High flow nasal cannula 609 provides nasal high flow therapy to thepatient illustrated. As the patient exhales, expired gas 603 is stillpushed to the ambient air. However, the high flow cannula 609 provides aflow of air into the respiratory system of the patient. As can be seenin FIG. 6B, this results in a lower overall CO2 concentration in atleast a portion of the dead space. For example, at locations 611, theair in the dead space cavities has a generally light color to indicate alower CO₂ content. Although some higher CO₂ content air is stillresidual, for example at 613, the overall CO₂ level of the residual airis lower. This leads to an overall higher O₂ concentration on the nextinspired breath of the patient.

The high flow therapy device can be configured to stabilize CSR bytransiently supplying high flow during a cycle of periodic breathing. Asdiscussed above, it is believed that carotid chemoreceptors aresensitive, fast-responding CO₂ sensors and it is believed they areimportant in the initiation of apnea in response to a single ventilatoryovershoot. The response to changes in PaCO₂ by the carotidchemoreceptors are magnified in the presence of hypoxia. It is thoughtthat the contribution of peripheral chemosensitivity to increases inventilation is about 25% in normoxia and about 70% in hypoxia(SaO2=75%). During the hypopnea phase of CSR, PaO₂ decreases and PaCO₂increases. The decrease in PaO₂ increases the respiratory systemsresponse to the increase in PaCO₂ and hence encourages hyperventilationwhich ultimately forms CSR. By supplying high flow therapy duringperiods of hypopnea, the drop in PaO₂ is potentially reduced and hencemay provide a stabilizing effect.

High flow therapy also increases Functional Residual Capacity (FRC) vialow levels of Positive End Expiratory Pressure (PEEP) which increasesoxygen and CO₂ stores. This decreases loop gain and hence alsopotentially helps to stabilize respiration. By turning the device offduring periods of hyperventilation the added inspiratory resistance canhelp to damp the hyperventilation. Finally, by reducing anatomicaldead-space through high flow therapy, changes in ventilation will morerapidly result in changes in PaCO₂ and PaO₂. This is analogous todecreasing delays in the system which may also promote stable breathing.

Thus, in an embodiment of the present system, CSR is treated by, forexample, (1) reducing the amount of hypoxia and reducing the potentialbuildup of PaCO₂ during a period of hypoventilation, and thereforereducing the likely of a ventilatory overshoot post hypopnea; (2)increasing FRC, which increases oxygen and CO₂ stores, which has astabilizing effect on respiration; (3) adding nasal resistance duringperiods of hyperventilation to dampen the hyperventilation; and (4)reducing anatomical dead-space through high flow therapy, whichpotentially reduces the delays in how ventilation affects PaCO₂ andPaO₂.

With reference to FIG. 7, a period of CSR cycles is shown on waveform701. Once appropriately identified, a high flow therapy (for examplenasal high flow therapy, “NHF”) can be periodically applied in order todampen the CSR cycle. Upon application of the high flow therapy, the CO₂build-up is limited, as shown in waveform 703, resulting in stabilizedCO₂ levels which will eventually lead to stabilized breathing.

With reference to FIG. 8, a transition between waxing and waning cyclesis determined (indicated as area 805) and high flow therapy (for examplenasal high flow therapy, “NHF”) is applied during this transitionperiod. In various embodiments, high flow therapy may stop afterrespiration amplitude begins to increase, for example, during the waxingtransition of the CSR cycle. Alternatively, high flow therapy cancontinue for a predetermined period of time, for example, as indicatedduring time 807 in FIG. 8. In additional embodiments, the period of highflow therapy is variable, based on, for example, the period of the CSRcycle or other attributes of respiration indicative of CSR. In anotherexample, an average breath volume or minute ventilation is calculatedover a period of time and high flow therapy is applied during breathsthat are below this threshold. In an embodiment, high flow therapy isapplied only during exhalation.

FIG. 9 illustrates a flow diagram of an embodiment of a high flowtherapy treatment for respiratory disorders, for example, including CSR.The therapy treatment process 920 begins by identifying a respiratorydisorder, for example, CSR at 921. At 923, transitions between waxingand waning breath cycles are determined. At 925, therapeutic high flowtherapy is applied. The high flow therapy can be applied as describedelsewhere herein, including for example, applying high flow therapybetween waxing and waning cycles, applying high flow therapyperiodically or for a period of time or during transitions cycles,applying high flow therapy during exhalation, or according to a phasedelay adjustment process as described in further detail below. At 927,the therapy effectiveness is evaluated. According to the evaluation, thetherapy is adjusted at 929 and the therapy process returns to 925, wherethe therapeutic high flow therapy is again applied.

The phase delay is a time delay from when the controller detects adecrease or increase in the tidal flow of the patients breathing to whenthe controller increases or decreases the flow of gases delivered to thepatient interface. In an embodiment, the phase delay tracks a delayperiod associated with the patient's chemoreceptors. Using the phasedelay, the controller controls the magnitude of the flow delivered tothe patient in an oscillatory fashion. The period of oscillationapproximates the period of oscillation of the patients breathing, forexample, between waxing and waning periods. In an embodiment, the shapeof the oscillatory gas delivery waveform may track the shape of theoscillatory breathing waveform of the patient. In an embodiment, thepeak flow delivered to the patient during the oscillatory flow profilemay be adjusted using a scaling factor with respect to the measureddifference between the maximum and minimum patient breathing tidalflows. In other embodiments, the peak flow can be a scaling factor fromthe maximum and/or minimum patient tidal flow. In an embodiment, thescaling factor can be constant throughout an entire cycle, or can beadjusted depending on whether the patient is in a waxing or waningperiod of the CSR cycle. For example, shallow breaths may require acertain flow while periods of hyperventilation may require adisproportionally different flow of therapy.

The phase delay applied by the controller may vary between about zerodegrees and about three hundred and sixty degrees. The phase delayapplied by the controller may vary between about zero degrees and aboutone hundred and eighty degrees. The phase delay applied by thecontroller may vary between about zero degrees and about ninety degrees.The phase delay applied by the controller may vary between about zerodegrees and about forty five degrees. The phase delay applied by thecontroller may vary between about zero degrees and about two hundred andseventy degrees.

In some embodiments, the application or adjustment of high flow therapyis applied using a series of incremental phase delays or phaseadvancements based on the CSR cycle. For example, during an initial CSRcycle, high flow therapy is applied at a first time. The first time maybe predetermined or it may be based on the identified CSR cycle and/oran observed chemoreceptor delay. During a subsequent CSR cycle, the highflow therapy is applied at a second time, which can be an incrementallyadvanced or delayed interval based on the CSR cycle. In other words, thesecond time is phase advanced or delayed from the first time. The amountof advancement or delay is based on the CSR cycle severity, the and/orbased on the effect of previous high flow therapy applications. In anembodiment, after each CSR cycle, the effect of previous high flowtherapy applications can be evaluated and optimal timing can bedetermined. The determination of phase delay application can be based onfeedback from the patient. After a period of phase delays has beenapplied, the effect of the treatment on the patient is evaluated todetermine if the phase delay is appropriate and is adjusted as needed inorder to respond to the patient's reaction to the treatment. In anembodiment, the phase delay is periodically reevaluated in accordancewith feedback from the patient.

In an embodiment, a pattern of incremental phase delays or advancementscan be applied. For example, if it is determined that a particular delayis effective, the timing of the high flow therapy is determined andapplied to gradually reduce the effects of CSR. In an embodiment, thesystem can apply a determined phase delay or advancement procedure overthe course of multiple CSR cycles and then evaluate the data to refinehigh flow therapy application. In an embodiment, the system can apply adetermined phase delay or advancement procedure over the course of aperiod of time, such as, for example, multiple nights or sessions. Forexample, in an embodiment, a first phase delay can be used for a firstperiod of time and a second phase delay can be used for a second orsubsequent period of time. In an embodiment, the phase delays can bepart of a series of predetermined profiles. After multiple time periods,the effect of each phase delay is evaluated and the optimal delay isselected and implemented upon detection of future CSR cycles. FIG. 10illustrates an embodiment of a phase delay procedure 1050 used to treatCSR cycles during high flow therapy. The procedure begins at 1051 wherethe patients CSR cycles are evaluated. At 1053, a phase delay procedureis determined based on the evaluation at 1051. At 1055, high flowtherapy is applied according to the phase delay procedure determinationat 1053. At 1057, after allowing the high flow therapy procedure to beapplied for a period of time, the procedure's effectiveness is evaluatedand adjusted as necessary. Once the evaluation at 1057 is completed, theprocedure returns to the 1055 where high flow therapy is again appliedaccording to the adjusted procedure of 1057

In some configurations, rather than adjusting flow rates, or in additionto adjusting flow rates, various mixtures of respiratory gasescontaining carbon dioxide and/or oxygen can be delivered from anexternal source with nasal high flow therapy, either continuously orperiodically to control respiration. The addition of CO₂ or O₂ into ahigh flow therapy mixture of air allows the system to adjust CO₂concentrations to help the body stabilize respiration. Thus, theaddition of CO₂ or O₂ into the gas mixture can be periodically effected,in accordance with the principals discussed above, in order to allow thebody to naturally regulate respiration.

In some configurations, the effects of a chosen therapy can be evaluatedand/or controlled using an external monitor that can be connected to aflow generator, using pressure, flow or a combination of pressure and/orflow changes in the nasal cavity, in the interface or anywhere betweenthe airways and the flow source. Such controls can be as described indetail in PCT Publication No. WO2013/172722, filed May 17, 2013, whichis hereby incorporated by reference in its entirety.

As described above, in some embodiments, a hybrid mask can be used totreat CSR or other respiratory disorders. In an embodiment, the hybridmask can be used as part of the CSR therapies described above, or it canbe used independently of the therapies described above. As noted above,some embodiments of hybrid masks are described in PCT PublicationWO2011/078703.

In an embodiment, a hybrid mask includes a nasal high flow componentwithin a non-sealing mask. The mask can be a nasal and/or oral mask. Thenasal high flow component directs a high flow of gas into the patient'snares. The high flow of gas is used to flush CO₂ from the patient'supper airway, including, for example, the patient's anatomical deadspace, that may not me completely expired during expiration. The highflow of gas may optionally be heated and/or humidified.

FIG. 11 illustrates an embodiment of a non-sealing mask 1101. Thenon-sealing mask portion is configured to contact the patient around thenose and/or mouth of the patient. For example, the mask can apply airflow to the nares using a conduit 1106 and/or prongs 1103. This maskportion creates a catchment 1102 that may collect expired CO₂. The nasalhigh flow can be adjusted or controlled to flush or remove CO₂ from theupper airway of the patient, as well as, or alternatively from onlyfrom, the catchment. As used herein, “non-sealing” is intended to meanthat the mask is configured to capture expired gas, but not seal so muchas to form a closed or sealed system. In this respect, the non-sealingmask should be able to allow gas from the nasal high flow to flow out ofthe mask without a significant increase in pressure to the patient thatmay inhibit expiration, yet still be capable of capturing expired CO₂from expiration. This non-sealing may be obtained, for example, throughadditional bias flow holes 905 or by configuring portions of the mask tobe spaced away from the patient's nose and/or mouth, for example asshown in FIG. 11.

The volume of a normal patient's nasal cavity portion of the anatomicaldead space in the upper airway is generally about 50 mL. Thus, thevolume of CO₂ collected within the nasal cavity is generally limited toapproximately the same amount of CO₂. In the embodiment shown in FIG.11, additional volume is provided which increases the volume of CO₂which is capable of being captured. For example, the hybrid mask asdepicted in FIG. 11 may provide as much as about 50 mL or more ofadditional volume. This allows for, for example, roughly double or moreof the volume of CO₂ to be collected than would naturally occur withoutintervention in the patient's upper airway. In other embodiments,additional or larger catchments, as described in greater detail below,may be provided which allow for hundreds of mL of CO₂ to be captured. Inan embodiment, the CO2 captured is in the range of 0 mL to 500 mL. In anembodiment, the range is about 25 mL to about 75 mL. In anotherembodiment, the range is about 100 mL to 200 mL. As would be understoodby those of skill in the art, different sized catchments can be used inorder to capture a desired amount of CO₂.

In this embodiment, when the nasal high flow is operating, CO₂ withinthe upper airway and the catchment is flushed or removed, or at leastreduced. This allows the patient to breathe fresh air, in particular,during initial inspiration.

Alternatively, the nasal high flow may be reduced or stopped. Thisallows expired CO₂ to collect in the catchment for rebreathing. Thecatchment CO₂, along with CO₂ remaining in the upper airway causes CO₂levels within the patient to increase. As such, in the presentlydescribed embodiment, the patient's CO₂ level can be controlled by highnasal flow. In particular, CO₂ level may be increased, when nasal highflow off or low, or decreased, when nasal high flow is on.

The presently described hybrid mask may be used in the treatment of CSRby controlling the amount of CO₂ available to the patient, thuscontrolling CO₂ levels within the patient. For example, during periodsof heavy breathing (waxing), CO₂ levels within the patient typicallyreduce, as CO₂ is rapidly expired as a result of the heavy breathing.However, the presently described hybrid mask allows for CO₂ expiredduring heavy breathing (waxing) to be collected in the catchment. Thisallows for rebreathing of expired CO₂, thus increasing CO₂ during aperiod where CO₂ levels typically decrease.

Additionally, for example, during periods of reduced breathing (waning),nasal high flow may be used to flush CO₂ from within the upper airway(anatomical dead space) as well as within the catchment. As a result,less CO₂ is available to the patient, thus CO₂ levels decrease during aperiod where CO₂ levels within the patient typically increase.

Accordingly, by controlling the amount of CO₂ available to the patientby way of nasal high flow and/or the hybrid masks described herein, CO₂levels of the patient may be controlled in order to trigger normalrespiration. Further, the application of nasal high flow may be adjustedto incorporate any phase delays associated with chemoreceptors throughthe patient.

In an embodiment, in addition to or alternatively to using a mask as aCO₂ entrapment, a reservoir can be used to hold expired CO₂ or airenriched CO₂. For example, a container, such as, for example, aninflatable bag, hood or other similar container can be used to act as areservoir to collect CO₂. In an embodiment, the container can be clearedfrom the expired air, expired air enriched by CO₂, or air enriched CO₂either by an increase of nasal high flow and/or additional flow throughthe reservoir.

Although many of the above embodiments describe the application of highflow therapy, it is to be understood that this language can encompassboth turning high therapy “on” from a zero flow applied state to a flowapplied state as well as increasing a flow rate from a lower flow rateto a higher flow rate.

Conditional language, such as, among others, “can,” “could,” “might,” or“may,” unless specifically stated otherwise, or otherwise understoodwithin the context as used, is generally intended to convey that certainembodiments include, while other embodiments do not include, certainfeatures, elements and/or steps. Thus, such conditional language is notgenerally intended to imply that features, elements and/or steps are inany way required for one or more embodiments or that one or moreembodiments necessarily include logic for deciding, with or without userinput or prompting, whether these features, elements and/or steps areincluded or are to be performed in any particular embodiment.

Any process descriptions, elements, or blocks in the flow diagramsdescribed herein and/or depicted in the attached figures should beunderstood as potentially representing modules, segments, or portions ofcode which include one or more executable instructions for implementingspecific logical functions or steps in the process. Alternateimplementations are included within the scope of the embodimentsdescribed herein in which elements or functions may be deleted, executedout of order from that shown or discussed, including substantiallyconcurrently or in reverse order, depending on the functionalityinvolved, as would be understood by those skilled in the art. It willfurther be appreciated that the data and/or components described abovemay be stored on a computer-readable medium and loaded into memory ofthe computing device using a drive mechanism associated with a computerreadable storing the computer executable components such as a CD-ROM,DVD-ROM, memory stick, or network interface. Further, the componentand/or data can be included in a single device or distributed in anymanner. Accordingly, general purpose computing devices may be configuredto implement the processes, algorithms and methodology of the presentdisclosure with the processing and/or execution of the various dataand/or components described above.

Although the present invention has been described in terms of certainembodiments, other embodiments apparent to those of ordinary skill inthe art also are within the scope of this invention. Thus, variouschanges and modifications may be made without departing from the spiritand scope of the invention. For instance, various components may berepositioned as desired. Moreover, not all of the features, aspects andadvantages are necessarily required to practice the present invention.Accordingly, the scope of the present invention is intended to bedefined only by the claims that follow.

What is claimed is:
 1. A high flow respiratory assistance systemcomprising: a flow source configured to provide a high flow ofrespiratory gases in order to administer high flow therapy; anon-sealing interface which prevents a significant increase in pressure,the non-sealing interface in fluid communication with the flow sourceand providing the high flow of respiratory gases in order to clear CO₂from anatomical dead space; a sensor configured to sense an indicationof a respiration and generate a respiration signal; a controller,wherein the controller: receives the respiration signal from the sensor,identifies respiration criteria based on the respiration signal, andcontrols the flow of gases by varying a target flow rate to delivernasal high flow based on the identification of the respiration criteria,the control of the flow of gases at the variable target flow rateconfigured to aid stabilization of respiration by increasing ordecreasing the flow rate to change the amount of CO₂ cleared from theanatomical dead space.
 2. The system of claim 1, further comprising ahumidifier in fluid communication with and between the flow source andthe interface.
 3. The system of claim 1, wherein the controlleridentifies respiration criteria by analysing an amplitude of therespiration signal for shallow breathing, apneas, heavy breathing, orhyperventilation.
 4. The system of claim 1, wherein the controlleridentifies respiration criteria by analysing the respiration signal forperiods of a waxing respiration portion and a waning respirationportion.
 5. The system of claim 1, wherein the controller controls theflow of gas by applying the high flow of respiratory gases during atransition between the waxing portion and the waning portion.
 6. Thesystem of claim 1, wherein the respiration criteria is a period andphases of the respiration signal.
 7. The system of claim 6, wherein thecontroller initiates nasal high flow during at least one of the phases.8. The system of claim 6, wherein the controller identifies a phasedelay associated with chemoreceptor signals.
 9. The system of claim 8,wherein the controller initiates nasal high flow based at least in parton the phase delay.
 10. The system of claim 3, wherein the controllerdetermines the respiratory criteria is indicative of Cheyne-StokesRespiration.
 11. The system of claim 10, wherein the controllerdetermines a periodic signal amplitude having a 90% reduction for 10seconds or more of a normal signal amplitude is indicative ofCheyne-Stokes Respiration.
 12. The system of claim 3, wherein thecontroller determines a periodic signal amplitude having a 50% reductionfrom a normal signal amplitude is indicative of Cheyne-StokesRespiration.
 13. The system of claim 12, wherein the controllerdetermines a periodic signal amplitude having a 50% reduction for 10seconds or more of a normal signal amplitude is indicative ofCheyne-Stokes Respiration.
 14. The system of claim 1, wherein the flowsource provides a high flow of respiratory gases of greater than 40litres per minute.
 15. The system of claim 1, wherein the non-sealinginterface is a nasal cannula.
 16. The system of claim 1, wherein thecontroller applies the flow of gas for a window of time less than orapproximately equal to a period of a Cheyne-Stokes Respiration cycle.17. A high flow respiratory assistance system comprising: a flow sourceconfigured to provide a high flow of respiratory gases in order toadminister high flow therapy; a non-sealing interface which prevents aincrease in pressure significant enough to inhibit expiration, thenon-sealing interface in fluid communication with the flow source andproviding the high flow of respiratory gases to in order to clearexpiratory gases from an airway; a sensor configured to sense anindication of flow, the indication of flow usable to determine arespiration; a controller, wherein the controller: receives theindication of flow and determines a respiration signal from the sensor,identifies respiration criteria based on the respiration signal, andcontrols the flow of gases by varying a target flow rate to delivernasal high flow based on the identification of the respiration criteria,the control of the flow of gases at the variable target flow rateconfigured to aid stabilization of respiration by increasing ordecreasing the flow rate to change the amount of CO₂ cleared from theanatomical dead space.
 18. The system of claim 17, wherein theexpiratory gases comprise exhaled CO2 that is not fully exhaled from theairway.
 19. The system of claim 17, wherein assisting respirationcomprises stabilizing respiration.
 20. The system of claim 17, whereinassisting respiration comprises lowering a flow rate whenhyperventilation is detected.
 21. The system of claim 17, wherein theairway is an anatomical dead space.